Amphibia occupy a crucial evolutionary position and therefore provide us with the opportunity to gain understanding of how the extraordinary complexity of mammalian immunity may have developed. I have been studying three species which offer a clear evolutionary and functional immunologic progression. My interest has centered primarily on the several regulatory roles of thymus-derived cells and macrophages. I plan to continue to explore T-cell regulation of antibody production in vitro by using specific lectins and antibodies for sorting and behavioral modulation. Our studies on immunologic regulatory changes during amphibian metamorphosis suggest that these models are especially well suited for tests of systemic (neuro-endocrine) control of different aspects of immune responses, e.g. antigen recognition, antibody production and particularly, thymic regulation. Additionally, amphibia, unlike mammals, affect much less subtle thymic regulation of responses to linear polysaccharides, e.g. Ficoll. Moreover, since amphibia can be more easily tolerized to these responses than others, they are useful for studying questions on self-tolerance. Since primitive vertebrates fail to respond to soluble protein antigens because of limited macrophage capacity, I plan to compare the capacities of primitive and more advanced amphibian macrophages to process and present antigen by using radiolabelled ovalbumin. My long term objectives are to understand the bases for mammalian immunologic failures by learning how their too finely tuned and fragile immune systems arose.